Medium-chain acyl-coenzyme A dehydrogenase deficiency

Episode of metabolic crisis

Patients with MCAD deficiency who went too long without eating or have an increased energy need, will get problems to produce the required amount of energy for their body and brain.
They will become sleepy, lethargic, comatose and, if not treated soon enough, they could die.

In the hospital the blood and urine of the patient presenting with a metabolic crisis can be investigated. Both urine and blood can contain specific substances that can point in the direction of a defect in fatty acid oxidation.
Because the fatty acid oxidation doesn't work properly, fatty acids cannot be burnt for energy and can accumulate or be further metabolised to other intermediates of the metabolism (also called metabolites).

In a patient with MCAD deficiency who is not having a metabolic crisis, these metabolites will not or barely be found, except maybe for acylcarnitine (see further).
Also not necessarily all metabolites will be found. A lot depends on the specific MCAD mutation, the circumstances and the seriousness of the metabolic crisis.

Here below is described what those metabolites and symptoms are (this is quite technical):

hypoglycemia: a patient with MCAD deficiency who is going through a metabolic crisis can have a too low blood sugar level because the body is not able to produce enough energy from body fats (see also the chapter about the fed-fast cycle). But this is certainly not always the case. Cases have been studied and described where the patient is going through en episode of metabolic crisis while the blood sugar level is normal.

hypoketonic: too low level of ketone bodies because they can not properly be produced from breaking down fats in the beta-oxidation process (see also the chapter on the fed-fast cycle). These ketone bodies can be found in the urine.
Some patients, however, suffer serious consequences of a metabolic crisis due to MCAD deficiency and at the same time do manage to produce ketone bodies. So this is also not an indicator on its own.

presence of many free fatty acids in the blood: because medium chain fatty acids (of length C8 and C10) can not be metabolised normally, an unusual high level of those can be found in the blood. This can also occur in patients with MCAD deficiency who are not going through a metabolic crisis.

dicarboxylic aciduria: if the beta-oxidation of fatty acids is not properly working, the body has an other process of fatty acid oxidation, called the omega-oxidation. This process will also not help to produce energy in patients with MCAD deficiency because the end product of omega-oxidation still has to be processed by beta-oxidation. It will leave metabolites in the urine. These are dicarboxylic acids of lengths C6, C8 and C10 (= medium chain).
If these metabolites are found in the urine together with an inappropriately low level of ketone bodies, than this is also a strong indication.

acylcarnitine in the blood, especially acylcarnitine with 8 carbons (see also the chapter on screening and the role of carnitine in the fat metabolism): patients with MCAD deficiency have a high amount of acylcarnitine of length C8, and possibly also a higher amount of length C6 and C10, in their blood. An acylcarnitine is a fatty acid combined with a carnitine. Carnitine behaves as transporter to get rid of the fatty acids that cannot be metabolised. Through the kidneys they end up in the urine of the patient as well.
A patient with MCAD deficiency, also one that is asymptomatic, will usually have a higher concentration of these in his blood.

presence of acylglycine in the urine: acylglycine is a fatty acid combined with a glycine. This is an other way of the body to get rid of the poisonous fatty acids (acyl-CoA) that cannot be burned. Just like with carnitine (see also the role of carnitine in the fat metabolism) the CoA is first removed and remains available for other chemical reactions.
The acylglycines hexanoylglycine and suberglycine can be found in the urine of a patient with MCAD deficiency going through a metabolic crisis. But also this is not always the case.

problems with the liver: the liver can me manually examined and might be enlarged. The liver plays an important roll in the fat metabolism in times of fasting and can be under great stress in times of a metabolic crisis. Other liver functions can also be checked in a blood sample. Those can indicate how much the liver is suffering from the metabolic crisis.

Patients for whom the diagnosis of MCAD deficiency was not yet made, can present themselves with some or all of the above symptoms.
This condition is what is called a metabolic crisis, or metabolic decompensation.

Patients for whom the diagnosis of MCAD deficiency was already made, should take the necessary precautions to avoid such a metabolic crisis. This kind of crisis can be very dangerous and can lead to permanent damage to for example the brain.
Read further about how MCAD deficiency is treated >

References

A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causesmild MCAD deficiency: a case report
Neonatal symptoms in medium chain acyl coenzyme A dehydrogenase deficiency [free registration required]
Morbidity and mortality in medium chain acyl coenzyme A dehydrogenase deficiency [free registration required]
The National Library of Medicine - MCAD deficiency
Fatty infiltration in the liver in medium chain acyl CoA dehydrogenase deficiency. [free registration required]
Outcome of medium chain acyl-CoA dehydrogenase deficiency after diagnosis [free registration required]
Medium chain acyl-CoA dehydrogenase deficiency
Medium-Chain Acyl-CoA Dehydrogenase Deficiency

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